Stroke is a major cause of disability and death worldwide. Oxygen and glucose deprivation (OGD) in brain tissue preparations can reproduce several pathological features induced by stroke providing a valuable ex vivo protocol for studying the mechanism of action of neuroprotective agents. Guanosine, an endogenous guanine nucleoside, promotes neuroprotection in vivo and in vitro models of neurotoxicity. We previously showed that guanosine protective effect was mimicked by inhibition of nitric oxide synthases (NOS) activity. This study was designed to investigate the involvement of nitric oxide (NO) in the mechanisms related to the protective role of guanosine in rat hippocampal slices subjected to OGD followed by reoxygenation (OGD/R). Guanosine (100 μM) and the pan-NOS inhibitor, l-NAME (1 mM) afforded protection to hippocampal slices subjected to OGD/R. The presence of NO donors, DETA-NO (800 μM) or SNP (5 μM) increased reactive species production, and abolished the protective effect of guanosine or l-NAME against OGD/R. Guanosine or l-NAME treatment prevented the impaired ATP production, lactate release, and glutamate uptake following OGD/R. The presence of a NO donor also abolished the beneficial effects of guanosine or l-NAME on bioenergetics and glutamate uptake. These results showed, for the first time, that guanosine may regulate cellular bioenergetics in hippocampal slices subjected to OGD/R injury by a mechanism that involves the modulation of NO levels.

中风是全世界残疾和死亡的主要原因。脑组织制剂中的氧气和葡萄糖剥夺 (OGD) 可以再现由中风引起的几种病理特征，为研究神经保护剂的作用机制提供了有价值的体外方案。鸟苷是一种内源性鸟嘌呤核苷，可在体内和体外神经毒性模型中促进神经保护。我们之前表明，鸟苷的保护作用是通过抑制一氧化氮合酶 (NOS) 活性来模拟的。本研究旨在调查一氧化氮 (NO) 在与鸟苷对大鼠海马切片进行 OGD 后复氧 (OGD/R) 的保护作用相关的机制中的作用。鸟苷 (100 μM) 和泛 NOS 抑制剂，l-NAME (1 mM) 为经受 OGD/R 的海马切片提供保护。NO 供体 DETA-NO (800 μM) 或 SNP (5 μM) 的存在增加了活性物质的产生，并消除了鸟苷或l- NAME 对 OGD/R 的保护作用。鸟苷或l- NAME 处理可防止 OGD/R 后 ATP 产生、乳酸释放和谷氨酸摄取受损。NO 供体的存在也消除了鸟苷或l- NAME 对生物能量学和谷氨酸摄取的有益作用。这些结果首次表明，鸟苷可能通过涉及调节 NO 水平的机制来调节遭受 OGD/R 损伤的海马切片中的细胞生物能量。